Several types of monoclonal antibodies (MoAb) with toxins have been under evaluation in two animal models: 1) the L10 hepatocellular carcinoma in syngeneic guinea pigs in which the conjugates were assessed against both primary and metastatic tumors and 2) a human melanoma in nude mice. Emphasis in these investigations involved determining optimal therapeutic doses of the immunoconjugates and single versus multiple treatments against established tumors and spontaneous metastasis. Immunoconjugate preparations of abrin (400-1120Mug's) and ricin (500 Mug's) A chains conjugated to D3 MoAb significantly delayed the growth of established L10 tumors and retarded the development of spontaneous axillary metastasis in guinea pigs. A single I.V. administration of a gelonin - D3 conjugate (100 Mug) significantly inhibited L10 tumor growth for up to 1 week. However, there was no effect on the development of axillary metastasis. A 9.2.27 MoAb reactive with a human melanoma either delayed or completely suppresed tumor growth in the prepalpable model, depending on the size of the original tumor inoculum in nude mice. In contrast, unconjugated MoAb had little or no effect on established palpable tumors. However, a 9.2.27 abrin A chain or gelonin conjugate significantly retarded the growth of established tumors. These studies are designed to give information for clinical trials with immunoconjugates.